Fabry disease

Background

Fabry disease is a rare genetic metabolic condition. It is
caused by changes (mutations) in the GLA gene, which provides
instructions for making an enzyme called alpha-galactosidase A.
Because of this there is a build-up of a fatty substance called
globotriaosylceramide (GL-3 or GB-3), in cells throughout the body,
particularly cells lining blood vessels in the skin and cells in
the kidneys, heart, and nervous system. Males with the condition
are usually more severely affected than females.

Credits

Last updated March 2016 by Dr D Hughes, Senior Lecturer in
Haematology, Royal Free London NHS Foundation Trust and University
College London, UK.

Although great care has been taken in the compilation and
preparation of all entries to ensure accuracy, we cannot accept
responsibility for any errors or omissions. Any medical information
is provided is for education/information purposes and is not
designed to replace medical advice by a qualified medical
professional.

What are the symptoms?

Symptoms of the classic form, in males with low activity of the
enzyme, usually become apparent in childhood or adolescence. They
include:

Gradual deterioration of kidney function usually occurs in men.
They may also develop heart problems such as an enlarged heart and
neurological problems, including stroke. Males with a higher level
of enzyme activity are more mildly affected. They show features
later in life, mostly with heart or kidney problems with few of the
other symptoms.

Females typically have milder symptoms at a later age of onset
than males. However, this is very variable. Some females may be
relatively asymptomatic (have no symptoms) throughout a normal life
span or may have symptoms as severe as those observed in males.

How is it diagnosed?

In males demonstration of low alpha-gal A activity in blood, or
skin cells that are grown in the laboratory (cultured) can make a
diagnosis. In females, measurement of alpha-galactosidase A
activity is unreliable. Molecular genetic testing of the gene
encoding the alpha-galactosidase A enzyme is the most reliable
method for identification of females with Fabry disease.

How is it treated?

The introduction of enzyme replacement therapy has offered the
opportunity to treat the underlying cause of Fabry disease.
Intravenous infusion of recombinant alpha-galactosidase An enzyme
has been shown to clear deposits of GB-3, stabilise kidney
function, reduce heart size and significantly improve pain and
quality of life. Enzyme is administered intravenously every two
weeks. In the UK most patients receive enzyme replacement at home.
Oral treatment is also approved and will be suitable for some
patients.

Other treatments can be given to relieve the symptoms of Fabry
disease. For example, nerve pain can be treated using antiepileptic
drugs such as gabapentin and carbamezapine. Angiokeratomas may be
removed or treated with laser therapy. Standard therapies such as
aspirin, antihypertensives, ace-inhibitors for protein in the urine
and anti-cholesterol agents are used to treat the renal (kidney),
cardiovascular and vascular symptoms of the disease.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Fabry disease is inherited in an X-linked manner. Affected
families should be referred to a genetics centre for information
and support.

Prenatal diagnosis
Prenatal testing is available for affected families by either
chorionic villus sampling (CVS) or amniocentesis. Preimplantation
genetic diagnosis may be available for families in which the
disease causing mutation has been identified.